1
00:00:03,990 --> 00:00:01,829
oh am i telling you anything you don't

2
00:00:05,590 --> 00:00:04,000
know no i'm not for those of you who

3
00:00:07,430 --> 00:00:05,600
walked in the mall you passed by those

4
00:00:08,790 --> 00:00:07,440
uh little candle shops and you're like

5
00:00:09,990 --> 00:00:08,800
wow there's got some nice odors coming

6
00:00:11,350 --> 00:00:10,000
out of you walk into the store and you

7
00:00:13,910 --> 00:00:11,360
start smelling the candles it's really

8
00:00:16,070 --> 00:00:13,920
nice so they got some really pretty

9
00:00:18,150 --> 00:00:16,080
smells in them various aldehydes maybe

10
00:00:21,510 --> 00:00:18,160
ketones and what's happening right now

11
00:00:22,950 --> 00:00:21,520
well you smell them but they're mostly

12
00:00:25,029 --> 00:00:22,960
most of these odorants are inside the

13
00:00:27,109 --> 00:00:25,039
candle they're held fast and the reason

14
00:00:29,429 --> 00:00:27,119
why they're held fast is because it's a

15
00:00:31,429 --> 00:00:29,439
solid and because it's a solid they're

16
00:00:33,590 --> 00:00:31,439
not diffusing out you want them to

17
00:00:35,910 --> 00:00:33,600
diffuse out what do you do

18
00:00:38,389 --> 00:00:35,920
you light it so if i had a candle up

19
00:00:40,310 --> 00:00:38,399
here maybe york and mark would be able

20
00:00:41,990 --> 00:00:40,320
to smell it but for the people in the

21
00:00:43,990 --> 00:00:42,000
back i'm gonna have to light this candle

22
00:00:45,510 --> 00:00:44,000
in five minutes everyone in this room is

23
00:00:47,510 --> 00:00:45,520
going to know exactly what odor is found

24
00:00:49,990 --> 00:00:47,520
in that candle what did i do i just

25
00:00:52,229 --> 00:00:50,000
changed the state i went from a solid to

26
00:00:54,549 --> 00:00:52,239
a liquid state the odorants now have an

27
00:00:56,549 --> 00:00:54,559
opportunity to release

28
00:00:59,510 --> 00:00:56,559
so how long does it take to diffuse

29
00:01:00,950 --> 00:00:59,520
through the wax it's not applicable

30
00:01:03,270 --> 00:01:00,960
it doesn't apply

31
00:01:05,030 --> 00:01:03,280
we're dealing with a solid so

32
00:01:07,510 --> 00:01:05,040
reasonably you could say it might take

33
00:01:09,750 --> 00:01:07,520
minutes under certain circumstances it

34
00:01:11,429 --> 00:01:09,760
might take hours there's literature

35
00:01:12,630 --> 00:01:11,439
saying that the pheromone sits for an

36
00:01:14,710 --> 00:01:12,640
hour and a half on the outside of the

37
00:01:16,310 --> 00:01:14,720
insects in cilla this would seem to be

38
00:01:18,469 --> 00:01:16,320
supported by the physical evidence right

39
00:01:20,149 --> 00:01:18,479
now and so this might take minutes to

40
00:01:23,109 --> 00:01:20,159
hours some of you might be saying well

41
00:01:24,630 --> 00:01:23,119
your presentation's over tom you're done

42
00:01:26,070 --> 00:01:24,640
your goal of one to ten milliseconds has

43
00:01:27,670 --> 00:01:26,080
been completely blown out of the water

44
00:01:28,950 --> 00:01:27,680
right now so why don't you just sit down

45
00:01:30,870 --> 00:01:28,960
however you can see i've got some other

46
00:01:33,350 --> 00:01:30,880
steps to go and york hasn't told me to

47
00:01:35,030 --> 00:01:33,360
sit down yet

48
00:01:37,270 --> 00:01:35,040
so what's our next step the next step is

49
00:01:38,710 --> 00:01:37,280
time to diffuse through the pores well

50
00:01:40,630 --> 00:01:38,720
it has to diffuse through the pores but

51
00:01:42,390 --> 00:01:40,640
has to get to the pores

52
00:01:45,990 --> 00:01:42,400
this is a representative syncilla

53
00:01:48,149 --> 00:01:46,000
trichodia from bombix mori the silkworm

54
00:01:50,389 --> 00:01:48,159
can you see the pores

55
00:01:51,190 --> 00:01:50,399
maybe not let me point them out to you

56
00:01:54,710 --> 00:01:51,200
one

57
00:01:56,389 --> 00:01:54,720
two three four this is drawn to scale

58
00:01:58,469 --> 00:01:56,399
this is drawn to scale so when the

59
00:02:01,429 --> 00:01:58,479
pheromone hits

60
00:02:04,069 --> 00:02:01,439
the syncilla tricodia most of them get

61
00:02:06,630 --> 00:02:04,079
stuck on the outside most of them don't

62
00:02:08,389 --> 00:02:06,640
go inside the pores and therefore most

63
00:02:11,430 --> 00:02:08,399
of them are going to have to migrate in

64
00:02:13,270 --> 00:02:11,440
some way through a solid crystalline

65
00:02:15,510 --> 00:02:13,280
waxy layer

66
00:02:17,510 --> 00:02:15,520
borderline impossible

67
00:02:19,270 --> 00:02:17,520
and so time to diffuse through the pores

68
00:02:21,190 --> 00:02:19,280
unknown no one's ever actually looked at

69
00:02:23,030 --> 00:02:21,200
anything like that before what about the

70
00:02:24,949 --> 00:02:23,040
time to bind a pheromone what's the

71
00:02:26,470 --> 00:02:24,959
process there well fortunately this has

72
00:02:29,430 --> 00:02:26,480
been looked at a little bit more the

73
00:02:31,270 --> 00:02:29,440
pheromone binding protein binds uh very

74
00:02:32,390 --> 00:02:31,280
well to the pheromone you put the

75
00:02:34,309 --> 00:02:32,400
pheromone binding protein and the

76
00:02:35,270 --> 00:02:34,319
pheromone together and they will become

77
00:02:37,589 --> 00:02:35,280
a couple

78
00:02:39,430 --> 00:02:37,599
like that so that's not a problem at all

79
00:02:41,350 --> 00:02:39,440
that'll turn about one millisecond so

80
00:02:43,509 --> 00:02:41,360
we're doing pretty good there

81
00:02:44,949 --> 00:02:43,519
time to transport the pheromone now

82
00:02:46,309 --> 00:02:44,959
remember it's not the pheromone that i'm

83
00:02:47,910 --> 00:02:46,319
transporting

84
00:02:50,390 --> 00:02:47,920
it's the pheromone and the pheromone

85
00:02:51,990 --> 00:02:50,400
binding protein because it's a complex

86
00:02:54,630 --> 00:02:52,000
and because it's a complex that's a big

87
00:02:56,790 --> 00:02:54,640
molecule the bigger the molecule the

88
00:02:58,390 --> 00:02:56,800
slower the diffusion so that's what i'm

89
00:02:59,270 --> 00:02:58,400
going to have to transport to the other

90
00:03:01,589 --> 00:02:59,280
side

91
00:03:03,670 --> 00:03:01,599
so i hit the literature 1993 broon and

92
00:03:05,190 --> 00:03:03,680
kim have a nice

93
00:03:07,190 --> 00:03:05,200
article that i can look at and make some

94
00:03:09,589 --> 00:03:07,200
extrapolations from predicting protein

95
00:03:11,270 --> 00:03:09,599
diffusion coefficients for those of you

96
00:03:13,030 --> 00:03:11,280
who may not be aware of this you have

97
00:03:15,270 --> 00:03:13,040
two different diffusion coefficients one

98
00:03:16,550 --> 00:03:15,280
is an air theater's in water so i'm

99
00:03:17,990 --> 00:03:16,560
interested in the one in water because

100
00:03:20,790 --> 00:03:18,000
that mostly closely resembles what i'm

101
00:03:22,390 --> 00:03:20,800
looking for so i take a look is it a rod

102
00:03:24,149 --> 00:03:22,400
or is it a globular protein mine's a

103
00:03:26,790 --> 00:03:24,159
globular protein it's about 14

104
00:03:28,710 --> 00:03:26,800
kilodaltons diffuses across my syncillar

105
00:03:30,070 --> 00:03:28,720
space i find out according to the

106
00:03:33,350 --> 00:03:30,080
literature it's going to take about 10

107
00:03:34,789 --> 00:03:33,360
to 12 milliseconds for that complex to

108
00:03:36,070 --> 00:03:34,799
make it across that space to the

109
00:03:38,070 --> 00:03:36,080
dendrite

110
00:03:39,670 --> 00:03:38,080
and boy did i make some big mistakes

111
00:03:41,910 --> 00:03:39,680
right now let me point them out to you

112
00:03:43,190 --> 00:03:41,920
for those of you who are not aware these

113
00:03:45,990 --> 00:03:43,200
are some of the mistakes i made some

114
00:03:47,750 --> 00:03:46,000
invalid assumptions with that one can i

115
00:03:49,509 --> 00:03:47,760
make a linear extrapolation the

116
00:03:51,430 --> 00:03:49,519
diffusion is a two dimensional molecule

117
00:03:53,670 --> 00:03:51,440
can i uh make a linear extrapolation to

118
00:03:55,589 --> 00:03:53,680
three no

119
00:03:56,789 --> 00:03:55,599
that there is a diffusion gradient i'm

120
00:03:58,149 --> 00:03:56,799
assuming that there's a diffusion

121
00:04:00,070 --> 00:03:58,159
gradient and there is not a diffusion

122
00:04:01,910 --> 00:04:00,080
gradient there is a much higher amount

123
00:04:03,750 --> 00:04:01,920
inside than there is outside so that's

124
00:04:05,509 --> 00:04:03,760
blown out of the water i'm assuming that

125
00:04:07,670 --> 00:04:05,519
there's a pure water solvent that's not

126
00:04:09,509 --> 00:04:07,680
pure water there's a lot of stuff in

127
00:04:11,670 --> 00:04:09,519
there and it is not pure water and

128
00:04:14,149 --> 00:04:11,680
therefore it becomes more like a gel as

129
00:04:16,069 --> 00:04:14,159
that individual last month told me about

130
00:04:18,069 --> 00:04:16,079
two i assume that no bound water

131
00:04:21,430 --> 00:04:18,079
molecules occur to the pbp or the

132
00:04:23,110 --> 00:04:21,440
pheromone binding protein well they do

133
00:04:24,790 --> 00:04:23,120
i assume that there's no dendritic

134
00:04:26,870 --> 00:04:24,800
sheath yes there's actually a sheath

135
00:04:28,070 --> 00:04:26,880
surrounding the dendrites that's also a

136
00:04:29,350 --> 00:04:28,080
problem how does the pheromone and the

137
00:04:31,270 --> 00:04:29,360
pheromone bonding protein get through

138
00:04:32,950 --> 00:04:31,280
that and i'm assuming that there's no

139
00:04:37,189 --> 00:04:32,960
change in temperature or viscosity over

140
00:04:38,629 --> 00:04:37,199
time all invalid assumptions

141
00:04:40,550 --> 00:04:38,639
so because i can't make this assumption

142
00:04:42,230 --> 00:04:40,560
why am i making this assumption at all

143
00:04:44,070 --> 00:04:42,240
well all i have to work with right now

144
00:04:46,629 --> 00:04:44,080
is 10 to 12 milliseconds there's no way

145
00:04:47,830 --> 00:04:46,639
to work with anything else so

146
00:04:49,270 --> 00:04:47,840
i'm just going to tell you right now the

147
00:04:52,469 --> 00:04:49,280
time to transport the pheromone is going

148
00:04:55,189 --> 00:04:52,479
to be a minimum of 10 milliseconds

149
00:04:57,030 --> 00:04:55,199
it doesn't matter to me i don't care

150
00:04:58,469 --> 00:04:57,040
whether or not it actually takes 11

151
00:05:04,070 --> 00:04:58,479
milliseconds

152
00:05:06,230 --> 00:05:04,080
i care about is that it's not faster

153
00:05:09,590 --> 00:05:06,240
than 10 milliseconds right now and that

154
00:05:11,830 --> 00:05:09,600
i can make with some certainty

155
00:05:13,749 --> 00:05:11,840
so uh the time to dissociate from the

156
00:05:15,990 --> 00:05:13,759
pheromone what about this has this been

157
00:05:17,430 --> 00:05:16,000
looked at fortunately it has

158
00:05:19,749 --> 00:05:17,440
time to dissociate from the pheromone

159
00:05:21,749 --> 00:05:19,759
how does this happen well uh we do know

160
00:05:23,749 --> 00:05:21,759
that it can dissociate but there are

161
00:05:24,790 --> 00:05:23,759
some problems as you might imagine

162
00:05:26,550 --> 00:05:24,800
there's been problems throughout my

163
00:05:28,390 --> 00:05:26,560
entire talk here's some more

164
00:05:30,310 --> 00:05:28,400
the problem is this once the pheromone

165
00:05:34,469 --> 00:05:30,320
binds with a pheromone binding protein

166
00:05:40,390 --> 00:05:37,990
it migrates across simple to understand

167
00:05:42,310 --> 00:05:40,400
and it binds to the purported receptor

168
00:05:44,390 --> 00:05:42,320
now it must associate well how does it

169
00:05:48,310 --> 00:05:44,400
do that

170
00:05:49,749 --> 00:05:48,320
dissociation only occurs at a ph of five

171
00:05:51,510 --> 00:05:49,759
there is no separation between the

172
00:05:54,710 --> 00:05:51,520
pheromone and the pheromone protein it

173
00:05:56,150 --> 00:05:54,720
binds strongly it binds so strongly that

174
00:05:57,270 --> 00:05:56,160
the germans carl casein that i talked

175
00:05:58,710 --> 00:05:57,280
about right now feels that it doesn't

176
00:06:00,230 --> 00:05:58,720
dissociate at all

177
00:06:02,230 --> 00:06:00,240
he actually feels the whole thing as a

178
00:06:04,629 --> 00:06:02,240
complex gets there because it really

179
00:06:06,950 --> 00:06:04,639
cannot dissociate however walter liel

180
00:06:10,550 --> 00:06:06,960
california ph of 5. this is how it

181
00:06:11,909 --> 00:06:10,560
separates well where is a ph of 5.

182
00:06:13,670 --> 00:06:11,919
does anyone have a ph of 5 running

183
00:06:15,270 --> 00:06:13,680
through their blood i hope not

184
00:06:17,590 --> 00:06:15,280
because you're not healthy

185
00:06:18,550 --> 00:06:17,600
so where's the physiological ph the ph

186
00:06:21,670 --> 00:06:18,560
of 5

187
00:06:23,590 --> 00:06:21,680
is located right here along the membrane

188
00:06:24,870 --> 00:06:23,600
so you must have contact with the

189
00:06:27,110 --> 00:06:24,880
membrane

190
00:06:30,070 --> 00:06:27,120
then the molecule recognizes it as being

191
00:06:32,309 --> 00:06:30,080
in a ph of 5 environment okay

192
00:06:34,390 --> 00:06:32,319
and then dissociation occurs and then it

193
00:06:35,749 --> 00:06:34,400
makes its way to the receptor

194
00:06:37,350 --> 00:06:35,759
well this is a little difficult to

195
00:06:39,670 --> 00:06:37,360
swallow but this is what's being

196
00:06:42,950 --> 00:06:39,680
reported right now

197
00:06:44,390 --> 00:06:42,960
and this occurs in nine milliseconds

198
00:06:46,710 --> 00:06:44,400
if

199
00:06:49,670 --> 00:06:46,720
we have a ph of five

200
00:06:51,990 --> 00:06:49,680
if we don't have a ph of five

201
00:06:54,629 --> 00:06:52,000
the half-life of dissociation is about

202
00:06:55,670 --> 00:06:54,639
100 seconds not milliseconds

203
00:06:57,430 --> 00:06:55,680
seconds

204
00:06:59,270 --> 00:06:57,440
this will not separate

205
00:07:01,430 --> 00:06:59,280
so do i go with the nine millisecond

206
00:07:02,469 --> 00:07:01,440
figure doesn't really matter as you can

207
00:07:05,990 --> 00:07:02,479
see right now

208
00:07:08,070 --> 00:07:06,000
or do i go with 100 second figure

209
00:07:09,990 --> 00:07:08,080
that's your choice and time to activate

210
00:07:11,350 --> 00:07:10,000
the receptor well that doesn't take long

211
00:07:13,510 --> 00:07:11,360
at all probably on the order of about 50

212
00:07:14,950 --> 00:07:13,520
picoseconds receptors activate pretty

213
00:07:17,270 --> 00:07:14,960
quickly so that's not really a major

214
00:07:19,110 --> 00:07:17,280
problem in the theory but we're dealing

215
00:07:21,990 --> 00:07:19,120
with something which is very very quick

216
00:07:26,950 --> 00:07:22,000
therefore significantly less than one

217
00:07:31,670 --> 00:07:29,430
and so some of you are not convinced

218
00:07:33,430 --> 00:07:31,680
why because you're the ssc

219
00:07:35,189 --> 00:07:33,440
because you're the ssc some of you are

220
00:07:36,469 --> 00:07:35,199
skeptical some of you are not buying

221
00:07:38,710 --> 00:07:36,479
what i'm telling you right now some of

222
00:07:39,830 --> 00:07:38,720
you are convinced thank you some of you

223
00:07:41,430 --> 00:07:39,840
are not

224
00:07:43,830 --> 00:07:41,440
but you're you might be a normal

225
00:07:45,189 --> 00:07:43,840
run-of-the-mill skeptic and that's fine

226
00:07:47,029 --> 00:07:45,199
some of you might be a pathological

227
00:07:48,150 --> 00:07:47,039
skeptic and i can't do anything for you

228
00:07:50,469 --> 00:07:48,160
but for you

229
00:07:52,950 --> 00:07:50,479
normal everyday run-of-the-mill skeptics

230
00:07:54,869 --> 00:07:52,960
right now i want you to chew on this

231
00:07:57,029 --> 00:07:54,879
take a look at neural transmitter

232
00:07:59,270 --> 00:07:57,039
synaptic transmission let's take a look

233
00:08:00,710 --> 00:07:59,280
and find out how long this process takes

234
00:08:03,110 --> 00:08:00,720
a process which has been known for

235
00:08:04,550 --> 00:08:03,120
decades and is exactly the same process

236
00:08:07,350 --> 00:08:04,560
that is being talked about in the

237
00:08:11,749 --> 00:08:09,350
one there's a major difference between

238
00:08:12,869 --> 00:08:11,759
the two the synapse the acetylcholine

239
00:08:14,469 --> 00:08:12,879
synapse that i'm talking about there's

240
00:08:16,550 --> 00:08:14,479
type 1 and type 2 receptors i'm talking

241
00:08:18,710 --> 00:08:16,560
about the one that's 20 nanometers long

242
00:08:21,589 --> 00:08:18,720
is going to diffuse over the course of

243
00:08:23,909 --> 00:08:21,599
20 nanometers my insect

244
00:08:27,270 --> 00:08:23,919
is diffusing over the course of between

245
00:08:29,670 --> 00:08:27,280
1150 to two thousand nanometers close

246
00:08:31,909 --> 00:08:29,680
one to two micrometers

247
00:08:33,110 --> 00:08:31,919
well that's a huge difference right now

248
00:08:34,230 --> 00:08:33,120
that would seem to make a difference

249
00:08:36,149 --> 00:08:34,240
right there but let's take a look at the

250
00:08:38,149 --> 00:08:36,159
time course of events arrival of the

251
00:08:40,310 --> 00:08:38,159
excitatory impulse again we'll assign

252
00:08:41,750 --> 00:08:40,320
that at zero milliseconds

253
00:08:44,070 --> 00:08:41,760
the binding of the vesicle to the

254
00:08:46,150 --> 00:08:44,080
membrane and release of neurotransmitter

255
00:08:48,550 --> 00:08:46,160
we have got it down to between three to

256
00:08:50,230 --> 00:08:48,560
five milliseconds right now so it's not

257
00:08:51,990 --> 00:08:50,240
faster than three and it's certainly not

258
00:08:53,430 --> 00:08:52,000
lower than five i think that the

259
00:08:54,389 --> 00:08:53,440
resolution might be worked out a little

260
00:08:56,310 --> 00:08:54,399
bit better and there may be some

261
00:08:57,750 --> 00:08:56,320
neurophysiologists who know more about

262
00:08:59,590 --> 00:08:57,760
this than i do but we're at three to

263
00:09:02,310 --> 00:08:59,600
five milliseconds right now

264
00:09:04,470 --> 00:09:02,320
diffusion across the synaptic cleft the

265
00:09:05,990 --> 00:09:04,480
20 nanometers and the binding of the

266
00:09:08,070 --> 00:09:06,000
neurotransmitter to the receptor they

267
00:09:10,949 --> 00:09:08,080
have not been able to separate all

268
00:09:12,230 --> 00:09:10,959
together that's 0.3 milliseconds take

269
00:09:16,150 --> 00:09:12,240
home message

270
00:09:17,990 --> 00:09:16,160
it takes 3.3 to 5.3 milliseconds for

271
00:09:19,430 --> 00:09:18,000
synaptic transmission

272
00:09:22,230 --> 00:09:19,440
and you're telling me

273
00:09:24,630 --> 00:09:22,240
that an insect is smelling as fast as

274
00:09:25,750 --> 00:09:24,640
synaptic transmission

275
00:09:30,070 --> 00:09:25,760
no

276
00:09:31,750 --> 00:09:30,080
so one of my conclusions well i think my

277
00:09:33,430 --> 00:09:31,760
conclusion should be obvious either the

278
00:09:34,870 --> 00:09:33,440
current theory of insectal faction needs

279
00:09:36,470 --> 00:09:34,880
to be modified

280
00:09:39,030 --> 00:09:36,480
in order to include one or more

281
00:09:40,550 --> 00:09:39,040
mechanisms in addition to simple

282
00:09:43,190 --> 00:09:40,560
diffusion because that's all i've got to

283
00:09:44,710 --> 00:09:43,200
work with right now simple diffusion or

284
00:09:46,750 --> 00:09:44,720
current theory needs to be replaced by a

285
00:09:49,430 --> 00:09:46,760
new theory that supports the

286
00:09:50,470 --> 00:09:49,440
electrophysiological or temporal

287
00:09:51,990 --> 00:09:50,480
data